He graduated fromin 1967 with a Bachelor of Arts degree in mathematics and received a Master of Science degree in computer science from in 1971, while he was also working full-time in ballistics for the U.S. Department of the Navy. Cain has authored four books: Leadership is Common Sense (1997), Speak as a Leader (1999), CEO of SELF (October 2001), and They Think You're Stupid (May 2005). He also authored an article titled "The Intangibles of Implementation" in the technical journal Interfaces (Vol. 9, No. 5, 1979, pp. 144-147), published by the Institute for Operations Research and the Management Sciences
After completing his master's degree from Purdue, Cain left the Department of the Navy and began working for The Coca-Cola Company as a business analyst. In 1977, he joined Pillsbury where he rose to the position of Vice President by the early 1980s. He left his executive post to work for Burger King – a Pillsbury subsidiary at the time – managing 400 stores in the area. Under Cain's leadership, his region went from the least profitable for Burger King to the most profitable in three years. This prompted Pillsbury to appoint him President and CEO of Godfather's Pizza, another of their then-subsidiaries. Within 14 months, Cain had taken Godfather's Pizza from 911 stores down to 420 stores and reduced costs significantly. As a result of his efforts Godfather's Pizza finally became profitable. In a leveraged buyout in 1988, Cain, Executive Vice-President and COO Ronald B. Gartlan and a group of investors bought Godfather's from Pillsbury. Cain continued as CEO until 1996, when he was asked to resign by the board. Later that year he became CEO of the National Restaurant Association – a trade group and lobby organization for the restaurant industry – where he had previously been chairman concurrently with his role at Godfather's.
Cain became a member of the board of directors to the Federal Reserve Bank of in 1992 and served as its chairman from January 1995 to August 1996, when he resigned to become active in national politics. Cain was a 1996 recipient of the Horatio Award.
Cain was on the board of directors of Aquila, Inc. from 1992 to 2008, and also served as a board member for Nabisco, Whirlpool, Reader's Digest, and AGCO, Inc.